Understanding and engineering membrane-protein interactions is of fundamental importance in biophysical chemistry since such interactions play key roles in processes such as viral infection, signal transduction, protein trafficking, and photosynthesis. This work aims to design a model peptide-membrane system to study the binding of monomeric a-helical peptides to membranes parallel to the surface of the membrane. Such binding is the first step in the insertion of a-helical membrane proteins and viral proteins into membranes. Nonetheless, unconfounded dissection of this process has been heretofore impossible because of the fine balance of self-association of peptides and membrane binding due to the hydrophobic effect. We havemade an initial design based on consideration of the forces and factors governing a-helicity, oligomerization, and membrane binding of peptides. Using an iterative approach, synthetic peptides will be characterized for structure (a-helicity in solution, oligomeric state in solution, and membrane-bound topology) and membrane binding. Mass spectrometry will be absolutely necessary to confirm the identity of the synthetic peptides.